Kazimierz Pasternak

Volatile Anesthetics Reduce Biochemical Markers of Brain Injury and Brain Magnesium Disorders in Patients Undergoing Coronary Artery Bypass Graft Surgery

OBJECTIVES Neuropsychological disorders are some of the most common complications of coronary artery bypass graft (CABG) surgery. The early diagnosis of postoperative brain damage is difficult and mainly based on the observation of specific brain injury markers. The aim of this study was to analyze the effects of volatile anesthesia (VA) on plasma total and ionized arteriovenous magnesium concentrations in the brain circulation (a-vtMg and a-viMg), plasma matrix metalloproteinase-9 (MMP-9), and glial fibrillary acidic protein (GFAP) in adult patients undergoing CABG surgery. DESIGN An observational study. SETTING The Department of Cardiac Surgery in a Medical University Hospital. PATIENTS AND METHODS Studied parameters were measured during surgery and in the early postoperative period. Patients were assigned to 3 groups: group O, patients who did not receive VA; group ISO, patients who received isoflurane; and group SEV, patients who received sevoflurane. RESULTS Ninety-two patients were examined. CABG surgery increased MMP-9 and GFAP. The highest MMP-9, GFAP, and the most dramatic disorders in a-vtMg and a-viMg were noted in group O. CONCLUSIONS Cardiac surgery increased plasma MMP-9 and GFAP concentrations. Changes in MMP-9, GFAP, and arteriovenous tMg and iMg were significantly higher in group O. Volatile anesthetics, such as ISO or SEV, reduced plasma MMP-9, GFAP concentrations, and disturbances in a-vtMg and a-viMg.

Crystal structure, antitumour and antimetastatic activities of disubstituted fused 1,2,4-triazinones

Molecular structure of 3,8-disubstituted 7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones (8-14) was confirmed by X-ray crystallography of 14. All the compounds were evaluated for their antitumour and antimetastatic activities in vitro. Furthermore, their cytotoxicities towards human normal cell line-HSF cells were established, allowing us to point out some structure-activity relationships. Among them, imidazotriazinone 12, revealing remarkable dose-dependent viability decreases in human myeloma RPMI 8226 cells, was found to be completely non-toxic towards normal HSF cells. In addition, heterobicycles 8-12 were proved to exhibit significant antimetastatic potentials in the motility assay.

Synthesis, structure elucidation, determination of the lipophilicity and identification of antitumour activities in vitro of novel 3-(2-furanyl)-8-aryl-7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones with a low cytotoxicity towards normal human skin fibroblast cells

Eleven novel 3-(2-furanyl)-8-aryl-7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones (12-22) were designed and obtained from appropriate 1-aryl-2-hydrazonoimidazolidines (1-11) by condensation reaction with 2-oxo-2-furanacetic acid and subsequent cyclocondensation of intermediate chain derivatives. IR, (1)H NMR and (13)C NMR spectra and elemental analyses confirmed the chemical structure of all the synthesized compounds. The reversed-phase HPLC method was optimized and proved to be applicable and reliable for the analysis of these unknown small molecules (12-22). These compounds were chromatographed on octadecyl silica (ODS) stationary phase and their hydrophobic parameters expressed as the log k(w) values were determined by RP-HPLC, using mixtures of methanol and water as mobile phases with different methanol concentrations. Octane-1-sulfonic acid sodium salt (OSA-Na) and 20% acetate buffer (pH 3.5) was added to the mobile phase (eluent containing 0.01 M/L OSA-Na in organic modifier (MeOH)-buffered mobile phase). The high values of regression coefficients (r >0.9841) for all the compounds investigated proved the excellent fit between experimental data and the Snyder-Soczewiński equation. Results obtained from the reversed-phase HPLC were compared both with those theoretically calculated and with those obtained from an ALOGPS 2.1. software by the use of nine different computational methods for estimation of log P. The predicted values of log P by use of AB log P algorithm revealed the best correlation with the experimental log k(w) values for the investigated solutes, since a good correlation (r=0.7760) between these quantities was found. The majority of novel imidazotriazinones were found to be evidently effective in vitro against human cancerous cells (HeLa and T47D) in an effective concentration of 50 μg/mL. Five compounds (13, 15, 16, 18 and 22) revealed remarkable antiproliferative activities and selective cytotoxicities for cancer cells over normal HSF cells. Therefore these ones may be considered as a basis for the design of novel useful non-toxic (13, 15 and 16) and low toxic (18 and 22) anticancer agents.

The changes in the antioxidant status of heart during experimental hypomagnesemia in balb/c mice

The present experiment was performed to assess if hypomagnesemia can influence antioxidant status in mice heart. The results could explain possibly a free radical theory of heart damage in magnesium deficiency. We used a rodent model of hypomagnesemia. The magnesium sufficient group received a standard diet whereas a magnesium deficient group received the diet containing a trace amount of magnesium. The activities of the most important antioxidant enzymes – catalase, glutathione peroxidase and superoxide dismutase were assessed in mice heart and liver in a time dependent manner, on the 10th and the 20th day of experiment. The level of magnesium in plasma of animals receiving the magnesium deficient diet dropped twice after the 8th day and four times after the 13th day and then reached a plateau value. The activity of catalase in heart in the magnesium deficient group increased gradually and was significantly (P<0.05) elevated by 27% on the 20th day of experiment whereas the superoxide dismutase activity was significantly decreased by 17% on the 20th day. Glutathione peroxidase activity was insignificantly elevated. The alterations of antioxidant enzyme activities in the heart indicate cardiomyocytess exposure to oxidative stress, which can be responsible for the cardiac lesions observed during hypomagnesemia.

Plasma matrix metalloproteinase 9 correlates with disorders of brain magnesium homeostasis in patients undergoing coronary artery bypass surgery

BACKGROUND Changes in plasma matrix metalloproteinase 9 (MMP-9) concentrations and parallel changes in brain magnesium homeostasis have not been examined in cardiac surgery patients. The purpose of the present study was to analyse these relationships in patients undergoing coronary artery bypass surgery (CABG) with extracorporeal circulation (ECC). Additionally, the effect of volatile anaesthetics was considered. PATIENTS AND METHODS Adult patients undergoing CABG with ECC under general anaesthesia were studied. Plasma MMP-9 and total (tMg) and ionized (iMg) magnesium concentrations were measured during surgery and during the early postoperative period. The plasma arteriovenous (a-v) tMg and iMg differences in the brain circulation were considered to be markers for brain magnesium homeostasis. The Mini-Mental State Examination test and computer tomography were used to diagnose postoperative neuropsychological disorders (PNPDs). RESULTS In total, 92 patients were examined. PNPDs were noted in 17 cases. Cardiac surgery resulted in increased plasma levels of MMP-9. The highest MMP-9 concentrations were observed in patients with PNPDs. MMP-9 concentrations strongly correlated with a-v tMg and a-v iMg differences. Compared with arterial measurements, venous tMg and iMg concentrations were higher during and immediately after surgery and lower during the early postoperative period. The most severe differences in a-v tMg and iMg were noted in patients with PNPDs. CONCLUSION 1. Cardiac surgery resulted in an increase in plasma MMP-9 concentrations. 2. This increase in MMP-9 was significantly greater in patients with PNPDs. 3. The plasma MMP-9 concentration was correlated with disorders of brain Mg homeostasis.

Antioxidants in patients receiving total parenteral nutrition after gastrointestinal cancer surgery.

Total parenteral nutrition (TPN) is essential for patients with postoperative impairing gastrointestinal function who are unable to receive and absorb oral/enteral feeding for at least 7 days. Oxidative stress plays a major role in the ethiopathogenesis of cancers. In this study, total antioxidant status (TAS), glutathione peroxidase (GPx), superoxide dismutase, malondialdehyde and ascorbic acid were studied in patients operated because of small intestine, colorectal or pancreatic cancer and subsequently receiving TPN in comparison with patients receiving standard nutrition after the operation. TAS level and GPx activity were decreased in patients with small intestine cancer but did not differ in patients with colorectal and pancreatic cancer before and after surgery. In all patient groups receiving TPN, superoxide dismutase activity after the surgery was kept at the same level as before. On the fifth day after the surgery, malondialdehyde concentration in each group was restored to the value observed before surgery. On the fifth day of TPN treatment, ascorbic acid concentration was increased in every group of patients.

Possible new organoselenium supplement – evaluation of its influence on the kidneys in comparison with inorganic sodium selenite

The aim of this work was to evaluate the possibility of using of the new selenoorganic ring compound, 3-(o-chlorobenzoylamino)-2-(o-tolylimino)-4-methyl-4-selenazoline, as a selenium supplement by investigating the influence of its short-term administration on Se accumulation and antioxidant status in kidney. For 10 days, adolescent male Wistar rats were treated with saline (control group), Na(2)SeO(3) (Se-IN group) or the studied compound (Se-ORG group) (5 x 10(-4) mg Se/g of once a day) via a stomach tube. The selenium concentration, total antioxidant status (TAS), activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), concentrations of ascorbic acid (AA) and reduced glutathione (GSH) and concentration of malonyldialdehyde (MDA) were determined in the kidney homogenates. TAS was significantly reduced in the Se-ORG group compared to the control. Reduced glutathione was markedly decreased in Se-treated animals compared to the control and in the Se-ORG group compared to the Se-IN group. Malonyldialdehyde was significantly increased in the Se-supplemented groups compared to the control group but considerably less so in the Se-ORG group. All other studied parameters displayed no significant differences. No increase in the accumulation of selenium and the partial impairment of the antioxidant status and enhancement of lipid peroxidation in the kidneys resulting from Se treatment could suggest that in the first period of administration, excess selenium was excreted with urine, leading to a disturbance of kidney functions. Comparison of the effect of our compound with that exerted by inorganic Na(2)SeO(3) suggests that the studied compound could be considered as a possible supplement after further investigations, including determination of selenium excretion with urine, as well as repetition of this study using a wide range of doses and periods of supplementation.